Process for separation of diamines and/or omega-aminoacids from a feed fixture

ABSTRACT

The present disclosure relates to methods for separating at least one amine chosen from diamines and omega-aminoacids from a feed mixture using a simulated moving bed (SMB) adsorptive technology.

This application claims priority to U.S. provisional application No.62/146,129, filed on Apr. 10, 2015, which is herein incorporated byreference in its entirety.

FIELD OF THE DISCLOSURE

The present disclosure relates to methods for separating at least oneamine chosen from diamines and omega-aminoacids (i.e., ω-aminoacids)from a feed mixture using a simulated moving bed (SMB) adsorptivetechnology.

SUMMARY OF THE DISCLOSURE

Diamines and/or ω-aminoacids can be used as monomers for synthesizing avariety of materials such as polyamide resins and fibers. For instance,hexamethylenediamine (HMD, a.k.a., 1,6-hexanediamine), a diamine, is achemical intermediate used in the production of nylon 6,6 via acondensation reaction with adipic acid. HMD is also used in theproduction of epoxy resins as well as the production of monomers forpolyurethanes. 7-aminoheptanoic acid (7-AHA), an ω-aminoacid, has beenused in the manufacture of nylon 7.

Commercial quantities of diamines or ω-aminoacids can be prepared viachemical methods. For example, a process of producing HMD comprises thesteps of subjecting butadiene to a hydrocyanation process in thepresence of nickel catalyst to produce adiponitrile, and hydrogenatingadiponitrile in the presence of a solid catalyst to yield HMD. At theend of that process, HMD needs to be separated from a mixture comprising6-aminocapronitrile, HMD, tetrahydrozaepine, adiponitrile, and lowboilers via, for example, by methods involving fractional distillation.See e.g., U.S. Patent Application No. 2006/0058555.

Further as an example, 7-AHA may be synthesized by reacting7-bromo-heptanoic acid with concentrated aqueous ammonia. That reactionmay result in a mixture comprising ammonium bromide and 7-AHA, which canbe separated by using ion-exchange resins.

A biological process such as fermentation process may be used to produceat least one amine chosen from diamines and ω-aminoacids. For example,U.S. Patent Application Publication Nos. 20130183728, 20130210090,20130217081, 20130224807, 20140186902, 20140242655, 20150004660, and2014/0199737 discloses biochemical pathways for producing HMD by formingone or two terminal functional groups, comprised of carboxyl, amine orhydroxyl group, in a C6 aliphatic backbone substrate; and U.S. PatentApplication Publication Nos. 20140193865 and 20140248673 disclosesbiochemical pathways for producing 7-AHA by forming two terminalfunctional groups, comprised of carboxyl, amine or hydroxyl group, in aC7 aliphatic backbone substrate.

Biological processes, however, frequently suffer from severallimitations including 1) a relatively small range of products; 2) lowyields, titers, and productivities; and 3) difficulty recovering andpurifying products from aqueous solutions. In particular, during therecovery step, techniques such as distillation, decantation, extraction,pervaporation, and chromatography have been employed. These methods,however, may be energy intensive, expensive to operate, and notpractical or economical for the recovery and purification of materialsfrom, for example, a fermentation broth.

Commercial applications of diamines and ω-aminoacids may require them tobe of very high purity with low quantities of impurities. Accordingly,it would be beneficial to be able to separate diamines and/orω-aminoacids produced in, for example, a commercial scale biologicalprocess in a simple and low-cost way.

The present disclosure provides methods for separating at least oneamine chosen from diamines and ω-aminoacids from a multi-componentmixture, such as a fermentation product, using a simulated moving bed(SMB) adsorptive technology.

SMB apparatuses suitable for separating the at least one amine from afeed mixture may comprise one or more separation zones. For example, aSMB may comprise only one zone to separate a desired product componentfrom other impurities when all of those impurities elute either fasteror slower than the desired product component. Further as an example, aSMB apparatus may comprise more than one separation zone, and thecomponents separated in each zone may have different polarities.

In one aspect, each zone may contain: one or more injection points for afeed mixture; one or more injection points for an eluent, the eluentcomprising, for example, an aqueous alcohol; a take-off point for anextract stream; and a take-off point for a raffinate stream. In oneaspect, part of the extract and/or raffinate streams can be recycledback into the same zone, and for example, the eluent and/or recyclestream may be adjusted such that the diamines and/or ω-aminoacids can beseparated from different components of the feed mixture each zone.

The present disclosure also relates to compositions comprising diaminesand/or ω-aminoacids, such as provided by the separation method disclosedherein.

DEFINITIONS

While mostly familiar to those versed in the art, the followingdefinitions are provided in the interest of clarity.

“Zone” refers to a system capable of accomplishing a binary separationcomprising: a plurality of chromatography columns, one or more injectionpoints for a feed mixture stream, one or more injection points for oneor more eluents, a raffinate take-off stream from which liquid can becollected from the plurality of chromatography columns, and an extracttake-off stream from which liquid can be collected from the plurality ofchromatography columns. In one aspect, each zone has only one injectionpoint for a feed stream. In another aspect, each zone has only oneinjection point for an eluent. In yet another aspect, each zone has twoor more injection points for different eluent.

“Raffinate” is the stream of components that move more rapidly with theliquid eluent phase compared with the solid adsorbent phase. As anexample, a raffinate stream can be enriched with more polar components,and depleted of less polar components compared with a feed stream.

“Extract” is the stream of components that move more rapidly with thesolid adsorbent phase compared with the liquid eluent phase. As anexample, an extract stream can be enriched with less polar components,and depleted of more polar components compared with a feed stream.

“Nonadjacent” when applied to columns in the same apparatus refers tocolumns separated by one or more columns, such as 3 or more columns,further such as 5 or more columns.

“SMB” means simulated moving bed adsorptive technology.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an exemplary SMB process for separating a binarymixture.

FIG. 2 illustrates an exemplary aspect for separating desired diamine(s)and/or ω-aminoacid(s) from faster and slower running components (i.e.more polar and less polar impurities).

FIG. 3 illustrates an exemplary aspect for separating desired diamine(s)and/or ω-aminoacid(s) from faster and slower running components (i.e.more polar and less polar impurities).

FIG. 4 illustrates an exemplary aspect for separating desired diamine(s)and/or ω-aminoacid(s) from faster and slower running components (i.e.more polar and less polar impurities).

FIG. 5 illustrates an exemplary aspect for separating desired diamine(s)and/or ω-aminoacid(s) from faster and slower running components (i.e.more polar and less polar impurities).

FIG. 6 illustrates an exemplary aspect for separating desired diamine(s)and/or ω-aminoacid(s) from faster and slower running components (i.e.more polar and less polar impurities).

FIG. 7 illustrates an exemplary aspect for separating desired diamine(s)and/or ω-aminoacid(s) from faster and slower running components (i.e.more polar and less polar impurities).

FIG. 8 illustrates an exemplary aspect for separating desired diamine(s)and/or ω-aminoacid(s) from faster and slower running components (i.e.more polar and less polar impurities).

FIG. 9 illustrates an exemplary aspect for separating desired diamine(s)and/or ω-aminoacid(s) from faster and slower running components (i.e.more polar and less polar impurities).

FIG. 10 illustrates an exemplary aspect for separating desireddiamine(s) and/or ω-aminoacid(s) from faster and slower runningcomponents (i.e. more polar and less polar impurities).

DETAILED DESCRIPTION OF CERTAIN ASPECTS

According to certain aspects, the present disclosure provides method forseparating at least one amine chosen from diamines and ω-aminoacids froma feed mixture.

In some aspects, the at least one amine may be chosen from C3-C12diamines and ω-aminoacids. In some aspects, the at least one amine maybe linear or branched. As a non-limiting example, the at least one aminemay be chosen from C5-C8 linear aliphatic a, ω-diamines, andω-aminoacids. In some aspects, the diamine is selected frompentamethylenediamine, hexamethylenediamine, heptamethylenediamine, and1,12-diaminododecane As a non-limiting example, the diamine may behexamethylenediamine (HMD, a.k.a., 1,6-hexanediamine, CAS #124-09-4). Insome aspects, the ω-aminoacid is an omega-aminocarboxylic acid, and inyet some aspects, the ω-aminoacid is selected from 5-aminopentaoic acid,6-aminocaporic acid, 7-aminoheptanoic acid, 11-aminounidecanoic acid, or12-aminolauric acid. Further as a non-limiting example, the ω-aminoacidmay be 7-aminoheptanoic acid (7-AHA, CAS #929-17-9).

In some aspects, the diamines and/or ω-aminoacids may be produceddirectly by a microorganism under suitable fermentation conditions. Insome aspects, the at least one amine may be produced indirectly bymicroorganism. For example, the microorganism may produce anintermediate component, which may subsequently be subject to one or moreprocessing steps to produce the desired diamine and/or ω-aminoacid suchas HMD or 7-AHA.

In some aspects, the feed mixture comprising at least one amine chosenfrom diamines and ω-aminoacids is an aqueous mixture.

In some aspects, the feed mixture comprising at least one amine chosenfrom diamines and ω-aminoacids may be from a chemical process such as apetrochemical process.

In some aspects, the feed mixture comprising at least one amine chosenfrom diamines and ω-aminoacids may be from a biological process. Forexample, the feed mixture may be produced from one or more processeschosen from fermentation, biomass extraction, biocatalytic, andenzymatic processes.

In some aspects, the feed mixture may be produced from a combinedchemical and biological process.

Fermentation Product

According to certain aspects, the processes disclosed in the presentdisclosure may be adaptable to a variety of biofermentation processes,for example, those suitable for large-scale industrial processes. Insome aspects, the fermentation product comprising at least one aminechosen from diamines and ω-aminoacids may be produced by batch,fed-batch, and/or continuous biofermentation.

Classical batch biofermentation is a closed system where the compositionof the broth is set at the beginning of the biofermentation and notsubjected to artificial alterations during the biofermentation. Thus, atthe beginning of the biofermentation the broth is inoculated with thedesired microorganism or organisms and biofermentation proceeds withoutfurther addition to the system. Typically, however, “batch”biofermentation is batch with respect to the addition of carbon sourceand attempts are often made at controlling factors such as pH and oxygenconcentration. In batch systems the metabolite and biomass compositionsof the system change constantly up to the time the biofermentation isstopped. Within batch cultures cells moderate through a static lag phaseto a high-growth log phase and finally to a stationary phase wheregrowth rate is diminished or halted. If untreated, cells in thestationary phase will eventually die. Cells in log phase generally areresponsible for the bulk of production of end product or intermediate,when the product is growth associated.

Fed-batch biofermentation processes comprise a typical batch system withthe exception that the substrate is added in increments as thebiofermentation progresses. Fed-batch systems are useful when cataboliterepression is apt to inhibit the metabolism of the cells and where it isdesirable to have limited amounts of substrate in the media.

In a continuous biofermentation system, a defined biofermentationsolution is added continuously to a bioreactor and an equal amount ofbiofermentation solution is removed simultaneously for processing.Continuous biofermentation generally maintains the cultures at aconstant high density where cells are primarily in log phase growth. Themethodology allows modulation of one factor or any number of factorsthat affect cell growth or end product concentration. For example, onemethod will maintain a limiting nutrient such as the carbon source ornitrogen level at a fixed rate and allow all other parameters tomoderate. In other systems a number of factors affecting growth can bealtered continuously while the cell concentration, measured by mediaturbidity, is kept constant. Continuous systems strive to operate understeady state growth conditions and balance cell loss due tobiofermentation solution being drawn off against cell growth rate in thebiofermentation.

Materials and methods known to those skilled in the art of microbiologyor biofermentation science may be adapted for generating a fermentationproduct comprising at least one amine chosen from diamines andω-aminoacids.

In some embodiment, the fermentation product can be produced byprokaryote host, eukaryote host, or both. The prokaryotic host can be,as non-limiting examples, from the genus Escherichia such as Escherichiacoli; from the genus Clostridia such as Clostridium ljungdahlii,Clostridium autoethanogenum, or Clostridium kluyveri; from the genusCorynebacteria such as Corynebacterium glutamicum; from the genusCupriavidus such as Cupriavidus necator or Cupriavidusmetallidurans;from the genus Pseudomonas such as Pseudomonas fluorescens, Pseudomonasputida or Pseudomonas oleavorans; from the genus Delftia acidovorans,from the genus Bacillus such as Bacillus subtillis; from the genesLactobacillus such as Lactobacillus delbrueckii; from the genusLactococcus such as Lactococcus lactis; or from the genus Rhodococcussuch as Rhodococcus equi. The eukaryotic host can be, as non-limitingexamples, from the genus Aspergillus such as Aspergillus niger; from thegenus Saccharomyces such as Saccharomyces cerevisiae; from the genusPichia such as Pichia pastoris; from the genus Yarrowia such as Yarrowialipolytica or from the genus Issatchenkia such as Issathenkiaorientalis; from the genus Debaryomyces such as Debaryomyces hansenii;from the genus Arxula such as Arxula adenoinivorans; or from the genusKluyveromyces such as Kluyveromyces lactis.

In some embodiments, the fermentation product disclosed herein can beproduced by Cupriavidus necator (C. necator).

In some aspects, the methods disclosed in U.S. Patent ApplicationPublication Nos. 20130183728, 20130210090, 20130217081, 20130224807,20140186902, 20140242655, 20150004660, and 2014/0199737 may be used forgenerating a fermentation product comprising HMD.

In some aspects, the methods disclosed in U.S. Patent ApplicationPublication Nos. 20140193865 and 20140248673 may be used for generatinga fermentation product comprising 7-AHA.

“Fermentation broth” refers to an aqueous solution produced directlyfrom batch, fed-batch, and/or continuous biofermentation vessel. Thefermentation broth may comprise microorganisms, at least one aminechosen from diamines and ω-aminoacids, metabolic intermediates, andother components such as salts, vitamins, amino acids, cofactors, andantibiotics.

In some aspects, the fermentation broth may be directly fed to a SMB forseparation of the at least one amine. In that case, the fermentationproduct fed into the SMB is the fermentation broth.

In some aspects, the fermentation broth may be subject to one or moretreatments, such as solid-liquid separation, prior to being fed into aSMB.

Various solid-liquid separation methods may be used to treatfermentation broth to product a fermenation product comprising at leastone amine chosen from diamines and ω-aminoacids. As non-limitingexamples, cross-flow filtration, centrifugation, and/or dead-endfiltration may be used to treat the fermentation broth to produce afermentation product comprising the at least one amine.

In one exemplary aspect, the fermentation broth may be subject to across-flow filtration unit that separates an influent stream into twoeffluent streams. The effluent that passes through a membrane is abiomass-free solution (or permeate) comprising at least one amine chosenfrom diamines and ω-aminoacids. The other effluent stream (or retentate)rejected by the membrane contains the cellular material of the biomassand the supernatant. This second biomass-containing effluent stream maybe immediately returned to a fermentation vessel.

Membrane suitable for cross-flow filtration depends on the size of theparticles to be removed from the influent stream. In one aspect,membranes with pore sizes about 0.2 micron and smaller, generally usedfor microfiltration and ultrafiltration, may be used. Further asnon-limiting examples, membranes comprising cellulosic, polyamide,polysulfone, and/or polyvinylidene fluoride may also be suitable forcross-flow filtration.

In addition to membrane selection, the combined effects of temperature,pressure, and contaminant fouling may need to be carefully considered toensure successful operation of a cross-flow filtration unit. Thechemical compatibility and membrane stability at a given process streampH may constitute additional factors to be considered. These conditionsmay be optimized readily by one skilled in the art.

In some aspects, the fermentation product that has been treated with asolid-liquid separation may be optionally subject to one or morefiltration steps. As a non-limiting example, the fermentation product,before being subjected to SMB, may be fed into a second stage cross-flowfiltration unit with more selective membranes or smaller pore sizes.This optional filtration would remove other components from thebiocatalyst-free solution, such as proteins, protein fragments, divalentsalts, monovalent ions, or organics. Using a second stage filtrationunit may potentially increase the life of the chromatographic adsorbent.

In some aspects, the fermentation product that will be fed into a SMBapparatus may comprise at least one amine chosen from diamines and/orw-aminoacids and at least one more polar component or at least one lesspolar component than the at least one amine. The less polar componentsmay have a stronger adherence to the adsorbent used as compared to thedesired diamines and/or ω-aminoacids product. During operation, suchless polar components may move with the solid adsorbent phase inpreference to the liquid eluent phase. The more polar components have aweaker adherence to the adsorbent used in the method of the presentdisclosure than does the diamines and/or ω-aminoacids product. Duringoperation, such more polar components may move with the liquid eluentphase in preference to the solid adsorbent phase. In some aspects, morepolar components will be separated into a raffinate stream, and lesspolar components will be separated into an extract stream.

Examples of the more and less polar components include (1) othercompounds from the manufacturing process (for example, other unwanteddiamines and/or ω-aminoacids, hydroxylated fatty acids, fatty acids,fatty acid esters, hydrocarbons, diacids, ω-hydroxyamines, orhydroxycarboxylic acids), (2) byproducts formed during storage, refiningand previous concentration steps, and (3) contaminants from solvents orreagents which are utilized during previous concentration orpurification steps.

Simulated Moving Bed (SMB)

A simulated moving bed (SMB) system suitable for separating at least oneamine from a feed mixture may comprise one zone or more than one zone.For example, a SMB may comprise only one zone to separate a desiredproduct component from other impurities when all of those impuritieselute either faster or slower than the desired product component.Further as an example, a SMB apparatus may comprise more than oneseparation zone, and the components separated in each zone may havedifferent polarities, or different affinities for a particularstationary phase or particular eluent. Each zone comprises a pluralityof chambers or columns, each of which contains a bed of solid adsorbentor mixture of solid adsorbents. Each zone may further comprise one ormore injection points for a feed mixture; one or more injection pointsfor an eluent, the eluent comprising, for example, an aqueous alcohol; atake-off point for an extract stream; and a take-off point for araffinate stream.

A zone can be broken down into sub-zones (also called sections inFIG. 1) where the columns in that sub-zone perform a particular portionof the separation, for example, adsorb A from feed, desorb B from thesolid adsorbent into eluent, etc.

The SMB may comprise one separation zone or a plurality of separationzones and may be further equipped with a plurality of inlet and outletports. For example, a SMB may comprise only one zone to separate adesired product component from impurities when all of those impuritieseither elute faster than or elute slower than the desired productcomponent. Further as an example, a SMB apparatus may comprise more thanone separation zone, and the components separated in each zone may havedifferent polarities.

The columns used in a SMB may be packed with a solid or mixture ofsolids having different adsorptivities for organic compounds and, thus,may be effective for separating at least one amine chosen from diaminesand ω-aminoacids from other compounds by selective adsorption. The SMBmay be equipped with a rotary valve or a plurality of valves arranged ina manner such that any feed stream may be introduced to any section orzone, and any outlet or effluent stream may be withdrawn from anysection or zone.

During operation of the SMB, the inlet connections to which the feedstreams are fed and the outlet connections from which the outlet streamsare withdrawn may be periodically moved, or indexed, from theirrespective columns to adjacent columns. For example, in one aspect, toachieve separation of at least one amine chosen from diamines andω-aminoacids, the locations of the inlet and outlet streams may be movedintermittently, from column to the next adjacent column, in thedirection of liquid eluent flow. The intermittent port movement in thedirection of liquid eluent flow simulates the counter-current movementof the bed or beds of the solid adsorbent. Different equipment andoperational strategies may be used to simulate the counter-currentmovement of the solid with respect to the liquid.

Any known simulated or actual moving bed chromatography apparatus may beutilized for the purposes of separating of diamines and ω-aminoacidsfrom a feed mixture such as a fermentation product. As non-limitingexamples, apparatuses described in U.S. Pat. No. 2,985,589, U.S. Pat.No. 3,696,107, U.S. Pat. No. 3,706,812, U.S. Pat. No. 3,761,533,FR-A-2103302, FR-A-2651148, FR-A-2651149, U.S. Pat. No. 6,979,402, U.S.Pat. No. 5,069,883 and U.S. Pat. No. 4,764,276, the contents of whichare herein incorporate by reference in their entirety, may be configuredand operated, according to the present disclosure, for separating ofdiamines and/or ω-aminoacids from a feed mixture such as a fermentationproduct.

An exemplary process of separating at least one amine from a feedmixture may be demonstrated via a process of separating a binary mixturein a single zone system illustrated in FIG. 1. A verticalchromatographic column containing stationary phase S may be divided intosections, such as into four superimposed sub-zones I, II, III and IVgoing from the bottom to the top of the column. The eluent is introducedat the bottom at IE by means of a pump P. The mixture of the componentsA and B which are to be separated is introduced at IA+B between sub-zoneII and sub-zone III. An extract containing mainly B is collected at SBbetween sub-zone I and sub-zone II, and a raffinate containing mainly Ais collected at SA between sub-zone III and sub-zone IV.

In the case of a simulated moving bed system, a simulated downwardmovement of the stationary phase S is caused by movement of theintroduction and collection points relative to the solid phase. In thecase of an actual moving bed system, downward movement of the stationaryphase S is caused by movement of the various chromatographic columnsrelative to the introduction and collection points. In FIG. 1, eluentflows upward and mixture A+B is injected between sub-zone II andsub-zone III. The components will move according to theirchromatographic interactions with the stationary phase, for exampleadsorption on a porous medium. The component B that exhibits strongeraffinity to the stationary phase (the slower running component) will bemore slowly entrained by the eluent and will follow it with delay. Thecomponent A that exhibits the weaker affinity to the stationary phase(the faster running component) will be easily entrained by the eluent.If the right set of parameters, especially the flow rate in each zone,are correctly estimated and controlled, the component A exhibiting theweaker affinity to the stationary phase will be collected betweensubzone III and sub-zone IV as a raffinate and the component Bexhibiting the stronger affinity to the stationary phase will becollected between sub-zone I and sub-zone II as an extract.

Adsorbents

Each chamber or column present in a SMB system comprises one or moreadsorbents having different adsorptivities for diamines and/orω-aminoacids. The terms “adsorption” or “adsorptivity”, as used herein,are intended to have the commonly understood meanings by persons skilledin the art, i.e., the tendency or affinity of gases, liquids, or solutesto accumulate on the surface of a solid or adsorbent. Similarly, terms“adsorbent”, “solid adsorbent”, and “stationary phase”, as used hereinin regards the adsorbent material contained within a SMB or otherchromatographic system, are intended to be synonymous and are usedinterchangeably.

The adsorbent or adsorbents used in the SMB may be selected on the basisof the at least one amine to be separated, the amount of water andsolvents present, the desorbent, components present in the feed mixture,and the desired separation.

In some aspects, more than one type of adsorbent may be used in the SMB.For example, the SMB may be packed with a mixture, such as a uniform orhomogenized mixture, of two or more solid materials. As another example,different adsorbent materials may be packed in differentlocations/columns/sub-zones/zones of the SMB. As another example, theSMB could use multiple adsorbents both as a mixture of adsorbents and indifferent locations within the SMB.

In one aspect, each chromatographic column in the SMB contains the sameadsorbent. In another aspect, each chromatographic column in the SMBcontains different adsorbents. In yet another aspect, when the SMBcontains multiple zones, chromatographic columns within a zone maycontain the same or different adsorbents. For example, each column inzone 1 may contain the same type of adsorbent that is different from theadsorbent contained in zone 2. Further as an example, each column inzone 1 may contain different types of adsorbent, but the same types ofadsorbent may be similarly used in different columns of zone 2.

Examples of suitable adsorbents include activated carbon, floridin,diatomite, molecular sieves, alumina, silica, silica-alumina, titania,polymeric resins containing one or more groups selected from sulfonate,hydroxy, amino, halogen, pyridyl, mono-substituted amino, disubstitutedamino, acyl, acyloxy, keto, alkoxy, and polymeric resins containingimmobilized silver or lead, commonly known as immobilized metal affinitycolumns (abbreviated herein as “IMAC”). Further examples of adsorbentsare Amberlite® XAD-4, XAD-7, and XAD-8 resins, available from Rohm &Haas Co.

In some aspects, the adsorption resin can be chosen from macroporousadsorption resins. For example, the macroporous adsorption resin can bechosen from nonpolar macroporous adsorption resins such as DOW XAD 418.Further as an example, the macroporous adsorption resin can be chosenfrom polar macroporous adsorption resins. In some aspects, thestationary phase comprises adsorption resin and at least one materialchosen from activated carbon, floridin, diatomite and silica gel. Insome aspects, the stationary phase is Orpheus silica-based stationaryphase adsorbent (manufactured by Orochem Technologies Inc., Naperville,Ill., USA).

The shape of the adsorbent material can be, for example, spherical ornonspherical beads. In some aspects, the adsorbent material can besubstantially spherical beads. Such beads can have a diameter of from 20to 500 microns, for example from 20 to 400 microns, from 30 to 3500microns, from 40 to 300 microns, from 50 to 250 microns, from 1000 to400 microns, or from 250 to 350 microns. In some circumstances, largerparticles may enable a lower pressure of eluent to be used in thesystem. This, in turn, has advantages in terms of cost savings,efficiency and lifetime of the apparatus.

In some aspects, the adsorbent can have a pore size of from 1 to 200 nm,2 to 150 nm, from 3 to 140 nm, from 4 to 130 nm, from 5 to 120 nm, 10 to120 nm, from 6 to 50 nm, from 15 to 45 nm, from 20 to 40 nm, from 25 to35 nm, from 6 to 20 nm, from 7 to 12 nm, or from 8 to 11 nm.

Eluent

The SMB may contain one or more eluents (desorbent) that are liquid orsolvent(s) capable of displacing a selectively adsorbed organic compoundfrom the adsorbent. The eluent may be a single solvent or a mixture ofsolvents. For example, the eluent may comprise at least one solventchosen from water, alcohols, diols, esters, nitriles, ketones, andethers.

In one aspect, the desorbent may be a straight- or branched-chain,unsubstituted or substituted alcohol, diol, ester, nitrile, ketone, orether containing up to about 10 carbon atoms. Non-limiting examples ofdesorbents may include methanol, ethanol, propanol, isopropanol, andbutanol; diols, such as ethylene glycol, 1,3-propanediol,1,2-propanediol, and 1,4-butanediol; nitriles, such as acetonitrile andbutyronitrile; ketones, such as acetone, methyl ethyl ketone, anddiethyl ketone; esters, such as methyl acetate, ethyl acetate, methylpropionate, and butyl acetate; and aliphatic and cyclic ethers, such asdimethyl ether, tetrahydrofuran, and dioxane.

In some aspects, the eluent can be an aqueous alcohol. The aqueousalcohol can comprise water and one or more short chain alcohols. Theshort chain alcohol can have from 1 to 6 carbon atoms. Non-limitingexamples of suitable alcohols include methanol, ethanol, n-propanol,i-propanol, n-butanol, i-butanol, s-butanol and t-butanol. In oneexemplary aspect, methanol and ethanol can be used. In yet anotherexemplary aspect, methanol can be used.

In some aspects, the average water:alcohol ratio of the eluent in theentire apparatus can be from 0.1:99.9 to 95:5 parts by volume, forexample from 0.1:99.9 to 9:91 parts by volume, from 0.2:99.8 to 7:93parts by volume, from 0.5:99.5 to 6:94 parts by volume, from 5:95 to20:80 parts by volume, from 50:50 to 95:5 parts by volume, from 30:70 to70:30 parts by volume, or from 30:70 to 50:50 parts by volume.

In some aspects where SMB contain more than one zone, the eluting powerof the eluent in each of the zones can be different. For example, theeluting power of the eluent in the first zone can be greater than thatof the eluent in the second and subsequent zones. In practice this canbe achieved by varying the relative amounts of water and alcohol in eachzone. Alcohols are generally more powerful desorbers than water. Thus,the amount of alcohol in the eluent in the first zone can be greaterthan the amount of alcohol in the eluent of the second and subsequentzones.

In some aspects, where the aqueous alcohol present in each zone has adifferent water alcohol content, the water:alcohol ratio of the eluentin the first zone can be from 0:100 to 5:95 parts by volume, for examplefrom 0.1:99.9 to 2.5:97.5 parts by volume, from 0.2:99.8 to 2:98 partsby volume, or from 0.5:99.5 to 1.5:98.5 parts by volume. Additionally,the water:alcohol ratio of the eluent in the second zone can be from3:97 to 7:93 parts by volume, from 4:96 to 6:94 parts by volume, or from4.5:95.5 to 5.5:94.5 parts by volume.

In one exemplary aspect, where the aqueous alcohol present in each zonehas a different water alcohol content, the water:alcohol ratio of theeluent in the first zone can be from 0.5:99.5 to 1.5:98.5 parts byvolume, and the water:alcohol ratio of the eluent in the second zone canbe from 4.5:95:5 to 5.5:94.5 parts by volume.

In some aspects where the rate at which liquid collected via the extractand raffinate streams in each zone is recycled back into the same zoneis adjusted such that diamines and/or ω-aminoacids can be separated fromdifferent components of the feed mixture in each zone, the water:alcoholratio of the eluents in each zone can be the same or different. Forexample, the water:alcohol ratio of the eluent in each zone can be from0.5:99.5 to 5.5:94.5 parts by volume. Further as an example, thewater:alcohol ratio of the eluent in the first zone can be lower thanthe water:alcohol ratio of the eluent in the second zone. Further asanother example, the water:alcohol ratio of the eluent in the first zonecan be higher than the water:alcohol ratio of the eluent in the secondzone. Also further as an example, the water:alcohol ratio of the eluentin the first zone can be the same as the water:alcohol ratio of theeluent in the second zone.

In some aspects, the ratios of water and alcohol in each zone referredto above are average ratios within the totality of the zone.

In some aspects, the water:alcohol ratio of the eluent in each zone canbe controlled by introducing water and/or alcohol into one or morecolumns in the zones. Thus, for example, to achieve a lowerwater:alcohol ratio in the first zone than in the second zone, water canbe introduced more slowly into the first zone than the second zone. Inanother example, essentially pure alcohol and essentially pure water canbe introduced at different points in each zone. The relative flow ratesof these two streams will determine the overall solvent profile acrossthe zone. In yet another example, different alcohol/water mixtures canbe introduced at different points in each zone. That will involveintroducing two or more different alcohol/water mixtures into the zone,each alcohol/water mixture having a different alcohol:water ratio. Therelative flow rates and relative concentrations of the alcohol/watermixtures in this aspect will determine the overall solvent profileacross the zone. In one non-limiting example, the water:alcohol ratio ofthe eluent in each zone is the same, i.e., the same alcohol/watermixture is introduced to each zone.

Zones

In some aspects, the SMB apparatus used for separating at least oneamine chosen from diamines and ω-aminoacids from a feed mixture maycomprise only one separation zone or may comprise a plurality ofseparation zones.

In one exemplary aspect, when the desired amine(s) to be separated fromthe feed mixture elute faster than or elute slower than other componentspresent in the feed mixture, the SMB may comprise only one zone.

In one exemplary aspect, two or more separation zones are used, forinstance, 2 to 5 separation zones may be used. In some aspects, thecomponents separated in each zone have different polarities. Each zonemay contain one or more injection points for a feed mixture; one or moreinjection points for an eluent, the eluent comprising, for example, anaqueous alcohol; a take-off point for an extract stream; and a take-offpoint for a raffinate stream. In one aspect, part of the extract and/orraffinate streams recycled back into the same zone, and for example, theeluent and/or recycle stream may be adjusted such that the diaminesand/or ω-aminoacids can be separated from different components of thefeed mixture in each zone.

In some aspects where the SMB has two zones, the process for separatingat least one amine chosen from diamines and ω-aminoacids from a feedmixture such as a fermentation product may comprise: introducing thefeed mixture to a SMB chromatography apparatus having a first zone and asecond zone, each of the first zone and the second zone comprising aplurality of linked chromatography columns, one or more eluent, anextract stream, and a raffinate stream collecting from the plurality oflinked chromatography columns.

In certain aspects, the raffinate stream enriched with more polarcomponents than the feed mixture and comprises the at least one amine iscollected from the first zone and subsequently introduced to anonadjacent column in the second zone. In one aspect, the at least oneamine is separated from compounds having higher polarity than the atleast one amine in the second zone.

In certain aspects, the raffinate stream enriched with less polarcomponents than the feed mixture and comprises the at least one amine iscollected from the first zone and subsequently introduced to a column,such as a nonadjacent column, in the second zone. In one aspect, the atleast one amine is separated from compounds having lower polarity thanthe at least one amine in the second zone.

In certain aspects, the raffinate stream enriched with higher polarcomponents than the feed mixture and comprises the at least one amine iscollected from the second zone and subsequently introduced to a column,such as a nonadjacent column, in the first zone. In one aspect, the atleast one amine is separated from compounds having higher polarity thanthe at least one amine in the first zone.

In certain aspects, the raffinate stream enriched with less polarcomponents than the feed mixture and comprises the at least one amine iscollected from the second zone and subsequently introduced to a column,such as a nonadjacent column, in the first zone. In one aspect, the atleast one amine is separated from compounds having lower polarity thanthe at least one amine in the first zone.

In certain aspects, the extract stream enriched with more polarcomponents than the feed mixture and comprises the at least one amine iscollected from the first zone and subsequently introduced to a column,such as a nonadjacent column, in the second zone. In one aspect, the atleast one amine is separated from compounds having higher polarity thanthe at least one amine in the second zone.

In certain aspects, the extract stream enriched with less polarcomponents than the feed mixture and comprises the at least one amine iscollected from the first zone and subsequently introduced to a column,such as a nonadjacent column, in the second zone. In one aspect, the atleast one amine is separated from compounds having lower polarity thanthe at least one amine in the second zone.

In certain aspects, the extract stream enriched with higher polarcomponents than the feed mixture and comprises the at least one amine iscollected from the second zone and subsequently introduced to a column,such as a nonadjacent column, in the first zone. In one aspect, the atleast one amine is separated from compounds having higher polarity thanthe at least one amine in the first zone.

In certain aspects, the extract stream enriched with less polarcomponents than the feed mixture and comprises the at least one amine iscollected from the second zone and subsequently introduced to a column,such as a nonadjacent column, in the first zone. In one aspect, the atleast one amine is separated from compounds having lower polarity thanthe at least one amine in the first zone.

In some aspects where the SMB has two zones, the eluent in the firstzone may contain more alcohol than the eluent in the second zone, andthe second zone is downstream of the first zone with respect to the flowof eluent in the system. Thus, the eluent in the system typically maymove from the first zone to the second zone. Conversely, the solidadsorbent phase typically moves from the second zone to the first zone.In one exemplary aspect, the two zones do not overlap, i.e. there are nochromatographic columns which are in both zones.

In some aspect, the SMB apparatus has a first zone, a second zone, and athird zone. In one non-limiting example where the eluent is aqueousalcohol, the water:alcohol ratios of the aqueous alcohol eluent presentin the first, second, and third zones may be different. As will beevident to one skilled in the art, this has the consequence thatimpurities having different polarities can be removed in each zone.

In some aspects where the SMB has three zones, the eluent in the firstzone can contain more alcohol than the eluent in the second zone and thethird zone, and the first zone is upstream of the second and third zoneswith respect to the flow of eluent in the system. For example, theeluent in the second zone contains more alcohol than the eluent in thethird zone and the second zone is upstream of the third zone withrespect to the flow of eluent in the system. Further as an example, inthe first zone, the diamines and/or ω-aminoacids product is separatedfrom components of the feed mixture which are less polar than thediamines and/or ω-aminoacids product. Also further as an example, in thesecond zone, the diamines and/or ω-aminoacids product is separated fromcomponents of the feed mixture which are less polar than the diaminesand/or ω-aminoacids product but more polar than the components separatedin the first zone. Further as an additional example, in the third zone,the diamines and/or ω-aminoacids product is separated from components ofthe feed mixture which are more polar than the at least one amine.

Columns

As noted above, SMB may comprise one or more separation zones, and insome aspects, each separation zone may comprise a plurality of linkedchromatography columns.

According to certain aspects, the total number of columns present in SMBmay range from 4 to 30 columns. For example, in one aspect, SMBapparatus may comprise 8 or more, for example 15 or more columns.Further as non-limiting examples, SMB apparatus may comprise 15 or 16columns, 19 or 20 columns, or 25 or 30 columns.

In some aspects, each zone may comprise approximately equal share of thetotal number of columns. For example, in the case of an apparatusconfigured with two zones, each zone may comprise approximately half ofthe total number of chromatographic columns in the system. The firstzone can comprise 4 or more, for example 8 or more, or about 8 columns.The second zone can comprise 4 or more, for example 7 or more, or about7 or 8 columns.

The dimensions of the columns used in the apparatus will depend on thevolume of feed mixture to be purified. According to certain aspects, thediameter of each column can range between 10 mm and 5 m, for examplebetween 5 mm and 500 mm, between 25 and 250 mm, between 50 and 100 mm,between 70 and 80 mm, between 0.5 m and 5 m, between 1 m and 4 m, orbetween 2 m and 5 m. According to certain aspects, the length (i.e.,height) of each column can be between 10 cm and 5 m, for example between10 and 200 cm, between 25 and 150 cm, between 70 and 110 cm, between 80and 100 cm, between 0.5 m and 5 m, between 1 m and 4 m, between 2 m and5 m, or between 3 m and 4 m.

The columns in each zone can have identical dimensions but may, forcertain applications, have different dimensions.

Flow Rates

The flow rates to the column may be limited by maximum pressures acrossthe series of columns and may depend on the column dimensions andparticle size of the solid phases. Larger diameter columns may needhigher flows to maintain linear flow through the columns.

In some aspects, for the typical column sizes outlined above, and for anapparatus having two zones, the flow rate of eluent into the first zonecan be from 1 to 3,000 L/min, for example from 1 to 4.5 L/min, from 1.5to 2.5 L/min, from 100 to 2,000 L/min, from 200 to 1,500 L/min, or from200 to 1,200 L/min. The flow rate of the extract from the first zone canbe from 0.1 to 1,000 L/min, for example from 0.1 to 2.5 L/min, from 0.5to 2.25 L/min, from 100 to 1,000 L/min, from 200 to 1,000 L/min, from100 to 400 L/min, or from 700 to 1,000 L/min. In one aspect where partof the extract from the first zone can be recycled back into the firstzone, the flow rate of recycle can be for example from 0.7 to 600 L/min,from 100 to 700 L/min, from 250 to 600 L/min, from 0.7 to 1.4 L/min, forexample about 1 L/min, about 375 L/min, about 80 L/min, or about 320L/min. The flow rate of the raffinate from the first zone can be from0.2 to 3,000 L/min, for example from 0.2 to 2.5 L/min, from 0.3 to 2.0L/min, from 100 to 3,000 L/min, from 200 to 3,000 L/min, from 400 to2,800 L/min, from 300 to 800 L/min, from 2,000 to 3,000 L/min. And inone aspect where part of the raffinate from the first zone can berecycled back into the first zone, the flow rate of recycle can be forexample from 0.3 to 1,200 L/min, from 100 to 1,200 L/min, from 0.3 to1.0 L/min, for example about 0.5 L/min, about 400 L/min, about 70 L/min,or about 350 L/min. In some aspects, the flow rate of introduction of afeed mixture such as a fermentation product into the first zone can befrom 5 mL to 3,000 L/min, for example from 5 to 150 mL/min, from 10 to100 mL/min, from 20 to 60 mL/min, from 100 to 3,000 L/min, from 200 to2600 L/min, or from 400 to 2500 L/min.

In some aspects, for the typical column sizes outlined above, and for anapparatus having two zones, the flow rate of eluent into the second zonecan be from 1 to 2,500 L/min, for example from 1 to 4 L/min, from 1.5 to3.5 L/min, from 100 to 2,000 L/min, from 200 to 1,500 L/min, or from 200to 1,200 L/min. The flow rate of the extract from the second zone can befrom 0.5 to 900 L/min, for example from 0.7 to 1.9 L/min, from 120 to900 L/min, from 200 to 800 L/min, from 100 to 400 L/min, or from 700 to1,000 L/min. In one aspect where part of the extract from the secondzone is recycled back into the second zone, the flow rate of recycle canbe for example from 0.6 to 600 L/min, from 200 to 600 L/min, from 0.6 to1.4 L/min, for example from 0.7 to 1.1 L/min, about 0.9 L/min, about 340L/min, about 70 L/min, or about 290 L/min. The flow rate of theraffinate from the second zone can be from 0.5 to 3,000 L/min, forexample from from 0.5 to 2.5 L/min, 0.7 to 1.8 L/min, about 1.4 L/min,from 100 to 3,000 L/min, from 200 to 3,000 L/min, from 400 to 2,800L/min, from 300 to 800 L/min, from 2,000 to 3,000 L/min.

In some aspects, part of one or more of the extract stream from thefirst zone, the raffinate stream from the first zone, the extract streamfrom the second zone, and the raffinate stream from the second zone canbe recycled back into the same zone, for example into an adjacent columnin the same zone.

This recycle is different from the feeding of an extract or raffinatestream into a non-adjacent column in another zone. Rather, the recycleinvolves feeding part of the extract or raffinate stream out of a zoneback into the same zone, for example into an adjacent column in the samezone.

In one aspect, the rate at which liquid collected via the extract orraffinate stream from the first or second zones is recycled back intothe same zone can be the rate at which liquid collected via that streamis fed back into the same zone, for example into an adjacent column inthe same zone. This can be seen with reference to FIG. 9. The rate ofrecycle of extract in the first zone is the rate at which extractcollected from the bottom of column 2 is fed into the top of column 3,i.e. the flow rate of liquid into the top of column 3. The rate ofrecycle of extract in the second zone is the rate at which extractcollected at the bottom of column 10 is fed into the top of column 11,i.e. the flow rate of liquid into the top of column 11.

In one aspect, recycle of the extract and/or raffinate streams can beeffected by feeding the liquid collected via that stream into acontainer, and then pumping an amount of that liquid from the containerback into the same zone. In this case, the rate of recycle of liquidcollected via a particular extract or raffinate stream, for example backinto an adjacent column in the same zone, is the rate at which liquid ispumped out of the container back into the same zone, for example into anadjacent column.

In one aspect, the amount of liquid being introduced into a zone via theeluent and feed streams is balanced with the amount of liquid removedfrom a zone, and recycled back into the same zone. Thus, with referenceto FIG. 9, for the extract stream, the flow rate of eluent (desorbent)into the first or second zone (D) is equal to the rate at which liquidcollected via the extract stream from that zone accumulates in acontainer (E1/E2) added to the rate at which extract is recycled backinto the same zone (D-E1/D-E2). For the raffinate stream in a zone, therate at which extract is recycled back into a zone (D-E1/D-E2) added tothe rate at which feed is introduced into a zone (F/R1) is equal to therate at which liquid collected via the raffinate stream from that zoneaccumulates in a container (R1/R2) added to the rate at which raffinateis recycled back into the same zone (D+F−E1−R1/D+R1−E2−R2).

In one aspect, the rate at which liquid collected from a particularextract or raffinate stream from a zone accumulates in a container canalso be thought of as the net rate of removal of that extract orraffinate stream from that zone.

In one aspect, the rate at which liquid collected via the extract streamout of the first zone is recycled back into the first zone can differfrom the rate at which liquid collected via the extract stream out ofthe second zone is recycled back into the second zone, and/or the rateat which liquid collected via the raffinate stream out of the first zoneis recycled back into the first zone can differ from the rate at whichliquid collected via the raffinate stream out of the second zone isrecycled back into the second zone.

In some aspects, varying the rate at which liquid collected via theextract and/or raffinate streams in each zone is recycled back into thesame zone has the effect of varying the amount of more polar and lesspolar components present in the other extract and raffinate streams.Thus, for example, a lower extract recycle rate results in fewer of theless polar components in that zone being carried through to theraffinate stream in that zone. A higher extract recycle rate results inmore of the less polar components in that zone being carried through tothe raffinate stream in that zone. This can be seen, for example, in thespecific aspect of the invention shown in FIG. 6. The rate at whichliquid collected via the extract stream in the first zone is recycledback into the same zone (D-E1) will affect to what extent any ofcomponent A is carried through to the raffinate stream in the first zone(R1).

In one aspect, the rate at which liquid collected via the extract streamfrom the first zone is recycled back into the first zone can be fasterthan the rate at which liquid collected via the extract stream from thesecond zone is recycled back into the second zone. As an example, araffinate stream containing the diamines and/or w-aminoacids producttogether with more polar components is collected from a column in thefirst zone and introduced to a nonadjacent column in the second zone,and the rate at which liquid collected via the extract stream from thefirst zone is recycled back into the first zone can be faster than therate at which liquid collected via the extract stream from the secondzone is recycled back into the second zone.

Further as an example, the rate at which liquid collected via theextract stream from the first zone is recycled back into the first zonecan be slower than the rate at which liquid collected via the extractstream from the second zone is recycled back into the second zone.

In one aspect, the rate at which liquid collected via the raffinatestream from the second zone is recycled back into the second zone can befaster than the rate at which liquid collected via the raffinate streamfrom the first zone is recycled back into the first zone. For example,an extract stream containing the diamines and/or w-aminoacids producttogether with less polar components can be collected from a column inthe second zone and introduced to a nonadjacent column in the firstzone, and the rate at which liquid collected via the raffinate streamfrom the second zone is recycled back into the second zone can be fasterthan the rate at which liquid collected via the raffinate stream fromthe first zone is recycled back into the first zone.

Further as an example, the rate at which liquid collected via theraffinate stream from the second zone is recycled back into the secondzone can be slower than the rate at which liquid collected via theraffinate stream from the first zone is recycled back into the firstzone.

In some aspects, the step time, i.e. the time between shifting thepoints of injection of the feed mixture and eluent, and the various takeoff points of the collected fractions depends on the number anddimensions of the columns used, and the flow rate through the apparatus.For example, the step time can be from 100 to 1200 seconds, such as from100 to 1000 seconds, from 200 to 800 seconds, or from about 250 to about750 seconds. Further as an example, the step time can be from 100 to 400seconds, or from 200 to 300 seconds, or about 250 seconds. Also furtheras an example, the step time can be from 600 to 900 seconds, or from 700to 800 seconds, or about 750 seconds. In other aspects, the step timecan be from 400 to about 800 seconds, from about 500 to 700 seconds, orabout 600 seconds.

The process for separating at least one amine chosen from diamines andω-aminoacids from a feed mixture such as a fermentation product may beoperated over a broad range of temperatures and pressure. In someaspects, the process can be conducted at from 15 to 65° C., for exampleat from 20 to 65° C., such as at 60° C. or from 30 to 55° C. In oneaspect, the process can be carried out at room temperature or atelevated temperatures. Pressure may not be a critical feature of theprocess. Thus, with the above ranges of temperature, pressures betweenabout 330 to about 3500 kPa gauge may be used. Typically, the pressurerange is between about 350 and 2000 kPa gauge.

In some aspects, for process for separating at least one amine chosenfrom diamines and ω-aminoacids from a feed mixture may comprise:introducing a feed mixture into one zone (for example the first zone) ofa SMB, collecting a first intermediate stream enriched with the diaminesand/or ω-aminoacids product and introducing the first intermediatestream into another zone (for example the second zone) of the SMB. Thus,in one aspect where the SMB system has two zones, the method involveseither (a) collecting a first intermediate stream from the first zoneand introducing it into the second zone, or (b) collecting a firstintermediate stream from the second zone and introducing it into thefirst zone. In this way, the diamines and/or w-aminoacids product can beseparated from both more and less polar components in a single method.

In one aspect, either (a) a raffinate stream containing the diaminesand/or ω-aminoacids product together with more polar components can becollected from a column in the first zone and introduced to anonadjacent column in the second zone, or (b) an extract streamcontaining the diamines and/or ω-aminoacids product together with lesspolar components can be collected from a column in the second zone andintroduced to a nonadjacent column in the first zone.

In some aspects, the SMB apparatus has two zones, and the method forseparating at least one amine chosen from diamines and ω-aminoacids froma feed mixture may comprise: (i) introducing the feed mixture into thefirst zone of the SMB, and removing a first raffinate stream enrichedwith the diamines and/or ω-aminoacids product and a first extract streamdepleted of the diamines and/or ω-aminoacids product, and (ii)introducing the first raffinate stream into the second zone, removing asecond raffinate stream depleted of the diamines and/or ω-aminoacidsproduct, and collecting a second extract stream to obtain the diaminesand/or ω-aminoacids product.

The aspects described immediately above are further illustrated in FIG.2. A feed mixture F comprising the diamines and/or ω-aminoacids product(B) and more polar (C) and less polar (A) components is introduced intothe first zone. In the first zone, the less polar components (A) areremoved as extract stream E1. The diamines and/or ω-aminoacids product(B) and more polar components (C) are removed as raffinate stream R1.Raffinate stream R1 is then introduced into the second zone. In thesecond zone, the more polar components (C) are removed as raffinatestream R2. The diamines and/or ω-aminoacids product (B) is collected asextract stream E2.

The aspects described above are illustrated in more detail in FIG. 4,which is identical to FIG. 2 except that the points of introduction ofthe alcohol desorbent (D) and water (W) into each zone are shown. Thealcohol desorbent (D) and water (W) together make up the eluent. The (D)phase can be essentially pure alcohol, but may, in certain aspects be analcohol/water mixture comprising mainly alcohol. The (W) phase can beessentially pure water, but may, in certain aspects be an alcohol/watermixture comprising mainly water, for example a 98% water/2% methanolmixture.

A further illustration of these aspects is shown in FIG. 6. Here thereis no separate water injection point, and instead an aqueous alcoholdesorbent is injected at (D).

The separation into raffinate and extract stream can be aided by varyingthe desorbing power of the eluent within each zone. This can be achievedby introducing the alcohol (or alcohol rich) component of the eluent andthe water (or water rich) component at different points in each zone.Thus, as an example, the alcohol is introduced upstream of the extracttake-off point and the water is introduced between the extract take-offpoint and the point of introduction of the feed into the zone, relativeto the flow of eluent in the system. This is shown in FIG. 4.

Alternatively, the separation can be aided by varying the rates at whichliquid collected via the extract and raffinate streams from the twozones is recycled back into the same zone.

For example, the rate at which liquid collected via the extract streamfrom the first zone is recycled back into the first zone may be fasterthan the rate at which liquid collected via the extract stream from thesecond zone is recycled back into the second zone; or the water:alcoholratio of the eluent in the first zone may be lower than that in thesecond zone.

In one aspect, the first raffinate stream in the first zone can beremoved downstream of the point of introduction of the feed mixture intothe first zone, with respect to the flow of eluent in the first zone.

In one aspect, the first extract stream in the first zone can be removedupstream of the point of introduction of the feed mixture into the firstzone, with respect to the flow of eluent in the first zone.

In one aspect, the second raffinate stream in the second zone can beremoved downstream of the point of introduction of the first raffinatestream into the second zone, with respect to the flow of eluent in thesecond zone.

In one aspect, the second extract stream in the second zone can becollected upstream of the point of introduction of the first raffinatestream into the second zone, with respect to the flow of eluent in thesecond zone.

In one aspect, the alcohol or aqueous alcohol can be introduced into thefirst zone upstream of the point of removal of the first extract stream,with respect to the flow of eluent in the first zone.

In one aspect where water is introduced into the first zone, the watercan be introduced into the first zone upstream of the point ofintroduction of the feed mixture but downstream of the point of removalof the first extract stream, with respect to the flow of eluent in thefirst zone.

In one aspect, the alcohol or aqueous alcohol can be introduced into thesecond zone upstream of the point of removal of the second extractstream, with respect to the flow of eluent in the second zone.

In one aspect, when water is introduced into the second zone, the watercan be introduced into the second zone upstream of the point ofintroduction of the first raffinate stream but downstream of the pointof removal of the second extract stream, with respect to the flow ofeluent in the second zone.

In some aspects, the SMB apparatus has two zones, and the method forseparating at least one amine chosen from diamines and ω-aminoacids froma feed mixture may comprise: (i) introducing the feed mixture into thesecond zone, and removing a first raffinate stream depleted of thediamines and/or ω-aminoacids product and a first extract stream enrichedin the diamines and/or ω-aminoacids product, and (ii) introducing thefirst extract stream into the first zone, removing a second extractstream depleted of the diamines and/or ω-aminoacids product, andcollecting a second raffinate stream to obtain the diamines and/orω-aminoacids product.

The aspects described immediately above are illustrated in FIG. 3. Afeed mixture F comprising the diamines and/or ω-aminoacids product (B)and more polar (C) and less polar (A) components is introduced into thesecond zone. In the second zone, the more polar components (C) areremoved as raffinate stream R1. The diamines and/or ω-aminoacids product(B) and less polar components (A) are collected as extract stream E1.Extract stream E1 is then introduced to the first zone. In the firstzone, the less polar components (A) are removed as extract stream E2.The diamines and/or ω-aminoacids product (B) is collected as raffinatestream R2.

These aspects are further illustrated in more detail in FIG. 5, which isidentical to FIG. 3 except that the points of introduction of the shortchain alcohol desorbent (D) and water (W) into each zone are shown. Asabove, the (D) phase can be essentially pure alcohol, but may, incertain aspects be an alcohol/water mixture comprising mainly alcohol.The (W) phase can be essentially pure water, but may, in certain aspectsbe an alcohol/water mixture comprising mainly water, for example a 98%water/2% methanol mixture.

A further illustration of these aspects is shown in FIG. 7. Here thereis no separate water injection point, and instead an aqueous alcoholdesorbent is injected at (D).

In one aspect, the rate at which liquid collected via the raffinatestream from the second zone is reintroduced into the second zone can befaster than the rate at which liquid collected via the raffinate streamfrom the first zone is reintroduced into the first zone; or thewater:alcohol ratio of the eluent in the first zone can be lower thanthat in the second zone.

In one aspect, the first raffinate stream in the second zone can beremoved downstream of the point of introduction of the feed mixture intothe second zone, with respect to the flow of eluent in the second zone.

In one aspect, the first extract stream in the second zone can becollected upstream of the point of introduction of the feed mixture intothe second zone, with respect to the flow of eluent in the second zone.

In one aspect, the second raffinate stream in the first zone can becollected downstream of the point of introduction of the first extractstream into the first zone, with respect to the flow of eluent in thefirst zone.

In one aspect, the second extract stream in the first zone can beremoved upstream of the point of introduction of the first extractstream into the first zone, with respect to the flow of eluent in thefirst zone.

In one aspect, the alcohol or aqueous alcohol can be introduced into thesecond zone upstream of the point of removal of the first extractstream, with respect to the flow of eluent in the second zone.

In one aspect where water is introduced into the second zone, the watercan be introduced into the second zone upstream of the point ofintroduction of the feed mixture but downstream of the point of removalof the first extract stream, with respect to the flow of eluent in thesecond zone.

In one aspect, the alcohol or aqueous alcohol can be introduced into thefirst zone upstream of the point of removal of the second extractstream, with respect to the flow of eluent in the first zone.

In one aspect where water is introduced into the first zone, the watercan be introduced into the first zone upstream of the point ofintroduction of the first raffinate stream but downstream of the pointof removal of the second extract stream, with respect to the flow ofeluent in the first zone.

In some aspects, the SMB apparatus may comprise a total of fifteenchromatographic columns. These are referred to as columns 1 to 15. Thefifteen columns are arranged in series so that the bottom of column 1 islinked to the top of column 2, the bottom of column 2 is linked to thetop of column 3 etc. This can optionally be via a holding container,with a recycle stream into the next column. The flow of eluent throughthe system is from column 1 to column 2 to column 3 etc. The flow ofadsorbent through the system is from column 15 to column 14 to column 13etc.

In one exemplary aspect, the SMB apparatus may comprise a total offifteen chromatographic columns in two zones: the first zone may consistof eight adjacent columns, columns 1 to 8, which are connected asdiscussed above; the second zone may consist of seven columns, columns 9to 15, which are connected as discussed above. Additionally, the bottomof column 8 in the first zone is linked to the top of column 9 in thesecond zone.

In some aspects, recovery of diamine or ω-aminoacid of interest (i.e.,the portion that ends up in the SMB “product” stream) could range from80 to 99% of the amount of diamine or ω-aminoacid of interest in the SMBfeed. In some aspects, after SMB separation, the purity of diamineand/or ω-aminoacid of interest, on an organics-only basis (i.e.,excluding desorbent and/or water), may range from about 85 to 99 wt %.

In some aspects, the diamine(s) and/or ω-aminoacid(s) recovered from SMBapparatus may be subject to one or more purification steps to furtherpurify the the target α,ω-diamine or ω-aminoacid and produce a purifiedproduct stream containing the target α,ω-diamine or ω-aminoacid. The oneor more purification steps may be chosen from, as non-limiting examples,evaporation, distillation, vacuum distillation, filtration, membraneseparation, crystallization, evaporative crystallization, and coolingcrystallization.

In a another aspect, when one or more components exhibit a much strongeraffinity for the stationary phase adsorbent (i.e., much slower runningcomponents) than the other components, the feed mixture comprising atleast one amine may be first introduced into a pre-treatment guard bedcontaining the stationary phase adsorbent to capture the much slowerrunning components, forming a guard bed effluent of treated feed that isreduced in the much slower running components. The treated feed mixtureis subsequently introduced into a SMB unit to separate the the at leastone amine from the other remaining components. In another aspect, twoparallel guard beds are employed, where one guard bed is operating toadsorb the much slower running components in the feed and produce atreated feed, while the other guard bed does not receive a feed and isinstead being regenerated by introducing a desorbent to desorb the muchslower running components from the stationary phase.

In another aspect, the guard bed can be extracted with a solvent toremove the slower running components. If the slower running componentssuch as other unwanted diamines and/or ω-aminoacids, hydroxylated fattyacids, fatty acids, fatty acid esters, hydrocarbons, diacids,w-hydroxyamines, or hydroxycarboxylic acids are unreacted startingmaterial or intermediates in the chemical or biological preparation ofdiamines and ω-aminoacids, the recovered slower running components,after removal of unwanted solvents, may be recycled back to the chemicalor biological processes.

In another aspect, the extract is fed to an extract desorbent recoverystep to recover desorbent and produce a treated extract that is reducedin desorbent. The specific type of separation step will depend on thephysical properties of the desorbent and other components in theextract. The extract desorbent recovery step can be selection from thenon-limiting group comprising evaporation, distillation,crystallization, vacuum crystallization, and cooling crystallization. Inone aspect, the desorbent that is recovered from the extract desorbentrecovery step is recycled to the SMB unit. In another aspect, thecomponents in the extract such as unwanted diamines and/or ω-aminoacids,hydroxylated fatty acids, fatty acids, fatty acid esters, hydrocarbons,diacids, w-hydroxyamines, or hydroxycarboxylic acids are unreactedstarting material or intermediates in the preparation of diacids may berecycled back to the chemical or biological processes.

In another aspect, the raffinate is fed to a raffinate desorbentrecovery step to recover desorbent and produce a treated raffinate thatis reduced in desorbent. The specific type of separation step willdepend on the physical properties of the desorbent and other componentsin the raffinate. The raffinate desorbent recovery step may comprise onefor more separation unit operations selected from the non-limiting groupcomprising evaporation, distillation, vacuum distillation, filtration,membrane separation, crystallization, evaporative crystallization, andcooling crystallization. In one aspect, the desorbent that is recoveredfrom the raffinate desorbent recovery step is recycled to the SMB unit.

In another aspect, the raffinate is fed to a water removal step toproduce treated raffinate that is reduced in water. The specific type ofwater removal step will depend on the nature of the components in theraffinate. The water removal step may comprise one or more separationunit operations selected from the non-limiting group comprisingevaporation, distillation, vacuum distillation, filtration, membraneseparation, crystallization, evaporative crystallization, and coolingcrystallization. In one aspect the water that is recovered from thewater removal step is recycled to the SMB unit. In one aspect the waterthat is recovered from the water removal step is recycled to afermentation step.

EXAMPLES Example 1

An aqueous feed mixture comprising 10 wt % hexamethylendiamine (HMD),0.5 wt % 6-hydroxyaminohexane (6-HAH), and 0.5 wt % 6-aminocaproic acid(6-ACA) is fed at a flow rate of 146,199 kg/hr to a SMB unit comprising15 columns. Each column contains an adsorbent bed 4 m in diameter by 4 min height of Orpheus silica-based stationary phase adsorbentmanufactured by Orochem Technologies Inc., Naperville, Ill., USA. Theadsorbent is chosen such that 6-HAH and 6-ACA have a stronger affinityfor the adsorbent than does HMD, thereby enabling recovering of amajority of the 6-HAH and 6-ACA in the extract, and a recovery of amajority of the HMD in the raffinate. A methanol desorbent (mobilephase) is fed to the SMB unit at a flow rate of 52,266 kg/hr. An extractis withdrawn from the SMB unit at a flow rate of 41,122 kg/hr. Araffinate is withdrawn from the SMB unit at a flow rate of 157,342kg/hr.

At a time t, the aqueous feed mixture is fed to column 10, the methanoldesorbent is fed to column 1, the extract is withdrawn from column 6,and the raffinate is withdrawn from column 14. Periodically, accordingto a step time, dt, the inlet and outlet flows are each shifted to thenext higher numbered column (i.e., in the direction of liquid flow),simulating an opposite movement of each stationary phase adsorbent bedto the next lower numbered column. Any inlet or outlet flow that waspreviously directed to or from column 15 moves to or from column 1. Inother words, at time t+dt, the aqueous feed mixture is fed to column 11,the methanol desorbent is fed to column 2, the extract is withdrawn fromcolumn 7, and the raffinate is withdrawn from column 15. The total cycletime for the 15-column SMB unit is 15×dt.

The step time, dt, is adjusted so that, at steady state, the compositionof the extract is 1.7 wt % 6-ACA, 1.5 wt % 6-HAH, 1.7 wt % HMD, 3.2 wt %water, and the remainder methanol; the composition of the raffinate is0.02 wt % 6-ACA, 0.07 wt % 6-AHA, 8.83 wt % HMD, 8.47 wt % methanol, andthe remainder water; the HMD recovery in the raffinate is 95% and HMDpurity in the raffinate is 99.0 wt % (on an solvent-free basis, i.e.,excluding methanol and water).

What is claimed is:
 1. A process for separating at least one amine froma feed mixture comprising: introducing a feed mixture comprising atleast one amine chosen from diamines and ω-aminoacids into a simulatedmoving bed apparatus to separate the at least one amine; and recoveringa composition comprising the at least one amine with a purity higherthan that in the feed mixture from the simulated moving bed apparatus.2. The process according to claim 1 further comprising: subjecting thefeed mixture to at least one solid-liquid separation prior tointroducing the feed mixture into the simulated moving bed apparatus. 3.The process according to claim 2, wherein the at least one solid-liquidseparation is chosen from cross-flow filtration, centrifugation, anddead-end filtration.
 4. The process according to claim 1, wherein thefeed mixture comprises a fermentation product.
 5. The process accordingto claim 4, wherein the fermentation product is produced by at least oneorganism chosen from Escherichia coli, Clostridium ljungdahlii,Clostridium autoethanogenum, Clostridium kluyveri, Corynebacteriumglutamicum, Cupriavidus necator, Cupriavidusmetallidurans, Pseudomonasfluorescens, Pseudomonas putida, Pseudomonas oleavorans, Delftiaacidovorans, Bacillus subtillis, Lactobacillus delbrueckii, Lactococcuslactis, Rhodococcus equi, Aspergillus niger; Saccharomyces cerevisiae,Pichia pastoris, Yarrowia lipolytica, Issathenkia orientalis,Debaryomyces hansenii, Arxula adenoinivorans, and Kluyveromyces lactis.6. The process according to claim 1, wherein the simulated moving bedapparatus comprises only one zone.
 7. The process according to claim 1,wherein the simulated moving bed apparatus comprises more than one zone.8. The process according to claim 7, further comprising collecting froma column in a zone a raffinate stream comprising the at least one amine,wherein a ratio of less polar to more polar components in the raffinatestream is increased or decreased relative to the feed mixture,introducing the raffinate stream into another zone; and recovering theat least one amine from said another zone.
 9. The process according toclaim 7, wherein collecting from a column in a zone an extract streamcomprising the at least one amine, wherein a ratio of less polar to morepolar components in the extract stream is increased or decreasedrelative to the feed mixture, introducing the extract stream intoanother zone; and recovering the at least one amine from said anotherzone.
 10. The process according to claim 8, wherein the raffinate streamis introduced into a column nonadjacent to the column from which theraffinate is collected.
 11. The process according to claim 9, whereinthe extract stream is introduced into a column nonadjacent to the columnfrom which the extract is collected.
 12. The process according to claim7, wherein part of an extract stream and/or a raffinate stream from onezone is/are recycled back into the same or different zone.
 13. Theprocess according to claim 1, wherein one or more eluents comprising atleast one solvent chosen from water and alcohol.
 14. The processaccording to claim 1, wherein the feed mixture comprises at least onediamine chosen from pentamethylenediamine, hexamethylenediamine,heptamethylenediamine, and 1,12-diaminododecane.
 15. The processaccording to claim 1, wherein the feed mixture comprises at least oneω-aminoacid chosen from 5-aminopentaoic acid, 6-aminocaporic acid,7-aminoheptanoic acid, 11-aminounidecanoic acid, and 12-aminolauricacid.
 16. The process according to claim 1 further comprising:subjecting the composition recovered from the simulated moving bedapparatus to at least one separation step.
 17. The process according toclaim 16, wherein the at least one separation step is chosen fromevaporation, distillation, vacuum distillation, filtration, membraneseparation, crystallization, evaporative crystallization, and coolingcrystallization.
 18. The process according to claim 1, wherein thesimulated moving bed apparatus comprises at least 4 columns.
 19. Theprocess according to claim 1, further comprising: introducing the feedmixture into at least one guard bed prior to introducing the feedmixture into the simulated moving bed apparatus.
 20. The processaccording to claim 1, further comprising: feeding into at least onedesorbent recovery process at least one raffinate stream and/or at leastone extract stream.
 21. The process according to claim 20, wherein theat least one desorbent recovery process is chosen from evaporation,distillation, crystallization, vacuum crystallization, and coolingcrystallization.
 23. The process according to claim 1, furthercomprising: feeding into at least one water recovery process at leastone raffinate stream.
 24. The process according to claim 23, wherein theat least one water recovery process is chosen from evaporation,distillation, vacuum distillation, filtration, membrane separation,crystallization, evaporative crystallization, and coolingcrystallization.